Chapter 18 Aldehydes and Ketones

Acid-Catalyzed Hydration of alkynes

• Reagent: HgSO4/H2SO4/H2O

• You need a Hg catalyst for terminal alkyne hydration.

• This reaction adds an OH with Markovnikov regioselectivity to form an enol.

• The enol product then tautomerizes to form a ketone.

Hydroboration-Oxidation of Alkynes

1. R2BH 2. H2O2, NaOH

anti-Markovnikov addition of water

The enol is tautomerized to make aldehydes

Primary alcohols are oxidized to aldehydes using

PCC/CH2CL2 or DMP/CH2CL2

Secondary alcohols are oxidized to ketones

With use of any oxidizing agent

Ex. PCC/CH2Cl2

Aldehydes and Ketones are formed from alkene with

Ozonolysis; 1.O3, CH2Cl2 2. (CH3)2S or Zinc and Water

Aldehydes are formed from 1-2 Cis Diols with Oxidative cleavage using

HIO4 periodic acid

Acid Chlorides are reduced by _____ to make aldehydes

1. LiAlH[OC(CH3)3]3 2. H2O

Acid Chlorides can react with _____ to give a ketone

R2CuLi, organocuprates (Gilman Reagents)

Esters are reduced by ______ to give an Aldehyde

DIBAL-H/H2O

Nitriles make ketones with

Addition of Grignard (R'MgX)/H2O or Organolithium (R'Li)/H2O reagents

Nitriles treated with______ followed by _____ forms Aldehydes

1. DIBAL-H 2. H2O

Friedel-Crafts Acylation of Benzene

Forms Ketones by treating a benzene ring with acid chloride (RCOCL) and AlCl3

Base-Catalyzed Mechanism

1) HO- + carbonyl

2) sp3 intermediate +H2O —-> R2C(OH)2

Good nucleophiles

nucleophile attacks the carbonyl group, cleaves pi bond and moves electron pair onto oxygen to form sp3 hybridized intermediate

Pronation of the negatively charged O atom by H2O forms addition product

Acid-Catalyzed Mechanism

1) H3O+ + carbonyl, pronation of carbonyl carbon

2) H2O + resonance-stabilized cation, nucleophilic attack to form positively charged intermediate

3)H2O + pos charged intermediate —> addition product, Deprotonation

poor nucleophiles

Addition of Gringard and organolithium reagents

Turns carbonyl oxygen into alcohol

R'MgX or R'Li, Ether/H2O

Addition of salts to terminal alkynes

H-C≡C- Na+/H2O

Forms alcohols that can be made into hydroxy aldehydes or hydroxy ketones

Formation of cyanohydrin

NaCN/H-A with aldehyde or ketone, adds HCN across carbon-oxygen pi bond to form cyanohydrin

Acid provides H+ for proton transfer to oxygen

Forming carboxyl group from cyanohydrin

Hydrolyzed by heating aq acid or base

H3O+/heat or Ar'/base

NaBH4

Mild reducing agent that reacts with aldehydes and ketones ONLY

Source of H-

LiAlH4

Strong reducing agent that reduces: aldehydes, ketones, carboxylic acids, esters, acid chlorides, and amides

Source of H-

Reducing Aldehydes and ketones

to alcohol, NaBH4 or LiAlH4 followed by proton action (H2O)

addition of H2 across the C=O

Formation of imine (Schaffer base)

Acid catalyst, NH3, RNH2, reacts with aldehydes and ketones

pH 4-5

addition-elimination reaction

Hydrolysis of Imine

Under acidic conditions, Imines hydrolyzed to aldehydes or ketones

H3O+

Formation of Enamines

Secondary amines react with aldehydes and ketones under mild acidic conditions (pH 4-5) forming enamines

H3O+

Addition of Oxygen Nucleophiles

Nucleophilic oxygen atom of water and alcohols can attack the carbonyl carbon atom of aldehydes and ketones to give addition products

Addition of water in presence of an acid or base

Aldehydes or ketones react with H2O to form a hydrate or germinal diol (gem-diol)

Reaction is reversible and amount of hydrate formed at equilibrium depends on the stabilization or destabilization of the carbonyl group

Base-nucleophile is -OH

Acid-nucleophile is H2O

Hydrates can be hydrolyzed to aldehydes or ketones with

H3O+

Aldehydes and ketones react with____ to form acetals

2 equivalents of alcohol

Acetal formation

Initial product is hemiacetal (unstable intermediate) that reacts with second equivalent alcohol to form acetal. R'C(OR)2R''

Common acid catalyst for acetal formation

TSOH

Acetal formation equilibrium can be driven to the right by

Removing H2O as it is formed due to Le Chatelier's principle

Acetals can be hydrolyzed to an aldehyde or ketone by

Treatment with aqueous acid

Aldehydes and ketones can be masked/protected by____ during chemical synthesis

Acetals

Step 1: Protection HOROH/TSOH

Step 2. Reduction LiAlH3, THF/H2O

Step 3: Deprotection H2O/H+

Witting Reaction

Synthesis of alkene from aldehydes and ketones using Ph3P-CH2

Generation of Phosphonium Ylide

1. Ph3P: + alkyl halide in SN2—-> Ph3PCH3halide

2. H- (NaH) + H-CH2-PPh3-Halide- ——> -CH2-PPh3+ Phosphonium ylide

Mechanism of Wittig Reaction

Step 1: Formation of oxasphosphetane

Step 2: Decomposition of oxaphosphetane to triphenylphosphine oxide and an alkene

Aldehydes are oxidized to carboxylic acids by

H2CrO4, K2Cr2O7/H2SO4

Ag(NH3)2+ in NH3/H2O

Tollens' Reagent

Ag(NH3)2+ in NH3/H2O

Oxidizes aldehydes to carboxylate anion

Reagents for reduction

H2/Pt or Ni

NaBH4/H2O

LiAlH4/H2O

Aldehydes are reduced to

Primary alcohols

Ketones are reduced to

Secondary alcohols

The carbonyl groups of aldyhydes and ketones can be reduced to _____

-CH2- groups

The Clemmensen Reduction

Zn(Hg), HCl, heat

The Wolff-Kishner Reduction

H2NNH2, KOH, heat

IR: ketone

1700 cm-1

IR: aldehydes

2 peaks 2850/2750 Fermi resonance

'HNMR: RCOCH2

2.2 ppm

'HNMR: RCOH

9.7-10pm

13CNMR C=O

200 ppm

Formaldehyde

Acetaldehyde

Benzaldehyde

Ethyl methyl ketone

Diethyl ketone

Propanone (acetone)

Acetophenone

benzophenone

Rules for naming aldehydes

-e changed to -al on parent alkane

CHO group bonded to ring- same ring and add -carbaldehyde

CHO group at C1

Rules for naming ketones

-e changed to -one on parent alkane

Always given carbonyl carbon lower number

IMF of aldehydes and ketones

LD and DD

Rule of 5

Aldehydes and ketones with less than or equal to 5 carbons are H2O soluble while those with more are insoluble